It is known for example from WO 2010/025469 to provide an aqueous composition (i.e. a composition based on water or another hydrophilic liquid that allows the formation of hydrogen bonds) comprising a biological antigen and an acrylic acid polymer (a biological antigen being an antigen derived from a living organism such as e.g. a bacterium, virus, animal, protist, fungus etc., typically a live or killed microorganism, or a biological molecule, preferably a protein or polysaccharide, derived from the living organism; the term “derived from” encompasses that the biological molecule itself or a precursor thereof is produced by the organism). The acrylic acid polymer in this prior art reference is used as an adjuvant, i.e a non-specific immunostimulating agent included in the composition to favor or amplify a particular process in the cascade of immunological events, ultimately leading to a better immunological response. Acrylic acid polymers have since long been recognized as safe and adequate adjuvants, capable of improving the immunological response to various types of antigens such as live or killed microorganisms, subunits of these organisms or recombinantly produced subunits such as proteins, polysaccharides and other types of molecules. For example, U.S. Pat. No. 3,178,350 already describes the use of an acrylic acid polymer as an adjuvant. These adjuvants are available under the trademark Carbopol™.
A notable property of acrylic acid polymers is that they significantly increase the viscosity of an aqueous composition since they inherently provide linked polymer chains in such compositions. The acid residues of the polymer chains namely may interact by hydrogen-bonding. Although hydrogen bonds are significantly less strong than covalent bonds, this interaction between the polymers chains may have a significant influence on the viscosity of the aqueous solution. This inherent property of acrylic acid polymers, which property is hardly depended on polymer chain length and type of side chains/groups, is widely used in for example creams or lotions where acrylic acid polymers are used as thickening agents. When the linked polymers form a true network of polymer chains throughout the composition (above a certain polymer concentration, typically above 0.2 to 0.5% w/w), and the interstices of the network are filled with the continuous phase, the composition is called a gel. For topical applications of aqueous compositions (such as hand creams, sun tan lotions) this is a preferred state of the composition. For compositions containing biological antigens, which compositions typically are administered via injection, the increase in viscosity is an important disadvantage. Even when the viscosity of the composition rises from about 5-70 mPas (which is typical for an aqueous composition comprising antigens) to about 200 mPas, this is very noticeable when applying the composition by injection (by hand) to a subject animal (the term animal in this specification and appended claims includes a human being). The gelling of the composition is commonly avoided at all times: gelled compositions cannot be readily injected. Therefore in practice, for compositions comprising biological antigens typically 0.1 to a maximum of 0.2% (weight over weight; w/w) of an acrylic acid polymer is applied. Indeed, in WO 2010/025469 which pertains to state-of-the art vaccines, 0.1% w/w of the acrylic acid polymer is applied. An example of a commercially available vaccine comprising an acrylic acid polymer is Suvaxyn™ M. Hyo—Parasuis (available from Pfizer Animal Health), which contains 0.2% (w/w) Carbopol™ 941.
It has been described in the art (U.S. Pat. No. 3,920,811) to add a physiologically acceptable electrolyte (i.e. a compound that ionizes when dissolved or molten to produce an electrically conductive medium), such as the electrolytes mentioned in column 4, lines 28-42 of the '811 patent) to an injectable composition in order to lower the viscosity of the composition to the point where they can be utilized commercially in a practical manner, while at the same time retaining the favorable adjuvant properties. As indicated however clearly in the '811 patent (column 7, lines 3-6), the electrolyte concentration may be as high as that which produces isotonicity in the final injectable solution of the mixture of the adjuvant solution and the biologic antigen. In particular, the actual injectable compositions are typically about one-half isotonic. The reason for this is that it is generally known that hypertonic solutions may provide tissue damage upon injection. Even when the composition is only slightly hypertonic and thus, the ultimate damage may be neglectable, the result of injection is that the animal may have a very uncomfortable feeling at the injection site, which may for example lead to stress, itching, biting etc. Therefore, in order to comply with the generally required safety standards for compositions for administration to animals, each commercially available composition comprising biological antigens and an acryl acid polymer, is at most isotonic with normal body fluid (e.g. serum), i.e. having an osmolarity of a 0.9% (w/v) sodium chloride solution in water (about 300 mOsm/l).